Bipolar Me

Causes of Depression: The Debate Continues

Earlier this month, I wrote about inflammation and a possible cause of mental illness and, in the process, mentioned some of the theories about what causes depression. Now I want to revisit the debate and the pros and cons of the various possible explanations.

The leading suggested causes are emotions (anger turned inward), genetics, trauma, brain chemistry, and now bodily causes such as cell disruptions and inflammation.

Anger turned inward and other emotional mechanisms never made a lot of sense to me, though in the course of my depression (later revealed to be the depressive phase of bipolar disorder), I certainly experienced a lot of anger that I wasn’t able to express. In fact, I denied that it even existed. The emotions most associated with depression for me at that time were guilt, shame, and hopelessness. There was a veritable stew of emotions I had turned inward, including anger, but it was far from the only one. Everyone who’s depressed has their own stew of emotions, which may also include fear, self-hatred, blame, and/or resignation. Any of those could turn inward as well, punishing their sufferers with depression.

Genetics makes more sense when you consider that depression and other mental disorders can run in families. But it also arises in families with no history of depression. Statistics say that if one family member experiences major depression, other family members—parents, children, and siblings—are 30% to 50% more likely to have it too. It’s even higher in twins.

Depression’s heritability is complicated, however. There’s not a specific depression gene, but some combination of elusive genes that combine to foster that tendency. What genes they are and how they interact with each other are among the problems still to be solved. And if genetics cause depression, what to do about it is still a mystery.

Trauma, PTSD, and C-PTSD have also been implicated in depression. That really rings true. Experiencing personal trauma or witnessing it again creates a stew of emotions, many long-lasting, which could easily cause depression. If you’re living with the after-effects. potentially for years, it’s easy to see how depression might result. The science of epigenetics may explain how the genes themselves change or how they are passed on to family members. The answers may involve several different mechanisms.

Brain chemistry is the most controversial of the hypotheses for the cause of depression. The theory is that certain neurotransmitters, such as serotonin, are deficient or not properly taken up by their receptors. However, Harvard Health Publishing has noted that “It’s often said that depression results from a chemical imbalance, but that figure of speech doesn’t capture how complex the disease is. Research suggests that depression doesn’t spring from simply having too much or too little of certain brain chemicals.” The major treatment has been to try to restore the balance with medication.

Part of the problem with this theory, however, is that no one is quite sure how these drugs work, only that they do—but not for every person with depression and not reliably. The most popular antidepressants are thought to work by improving the uptake of these brain chemicals. Until recently, improving these chemical “imbalances” was the primary treatment for depression, and it did a lot of good for a lot of people. But if the receptors are flooded with neurotransmitters right away, why do they take six weeks or more to take effect? Why do the results lessen over time to the point where antidepressants quit working for some patients? Why do they have no effect on others (treatment-resistant depression)?

Neurons/Cellular Interactions and Immune Disruptions are the latest avenues being explored. Research has focused on specific areas of the brain, such as the hippocampus, which is associated with both emotion and memory. Excitatory neurons, which change gene functions, and microglia, which microglia, the brain’s immune cells, become dysregulated and cause ongoing inflammation, which can affect the brain..

Also, Columbia University has shown for the first time that neurogenesis stalls in the brains of adults with major depressive disorder. They have identified the molecular programs that control neurogenesis, which may help researchers develop new therapies.

These new theories, while they present hope for understanding depression and the brain, are still a long way from reaching a consensus, or even agreement on the causative factors. That means they’re also a long way from developing new treatments for depression. Until they do, selective serotonin reuptake inhibitors (SSRIs) will likely continue to be the front line of therapy for major depression.